Bicycloheptane derivatives and process for preparing the same



United States Patent BICYCLOHEPTANE DERIVATIVES AND PROCESS FORPREPARING THE SAME Abraham Bavley, Brooklyn, and Charles J. Knuth,Forest Hills, N. Y., assignors to Chas. Pfizer & Co., Inc., Brooklyn, N.Y., a corporation of Delaware Application December 7, 1953, Serial No.396,752

7 Claims. (Cl. 260-455) No Drawing.

0 p LR, RCOS wherein R is alkyl; R1 is alkyl or alkoxy; and R2 ishydrogen, carboalkoxy or acylthio, R2 being hydrogen or acylthio when R1is alkyl, and carboalkoxy when R1 is alkoxy. R, R1 and R2 may containfrom 1 to 18 carbon atoms. Thus R and R1 may be methyl, ethyl, propyl,hexyl, decyl, octadecyl, etc.; R1 may also be methoxy, ethoxy,hexadecoxy and the like; R2 may be carbornethoxy, carboethoxy,carbobutoxy, carboheptadecoxy, or acetylthio, propionylthio,hexonylthio, heptadeconylthio, and so forth.

These compounds are prepared by the reaction of [2,2,1] bicyclohepteneswith an aliphatic thioacid, such as thioacetic acid, thiopropionic acid,thiobutyric acid, thioisobutyric acid and the like. The [2,2,1]bicycloheptenes are in turn prepared by the Diels-Alder reaction ordiene synthesis, a reaction well known in the art. To illustratefurther, various reactions between aliphatic thioficids and Diels-Alderadducts are hereinafter set fort For example, the reaction between analiphatic thioacid and a 2-acyl, bicyclo [2,2,1] heptene-S may bedescribed in the following manner: 1

/ COR acosn COR - RCOS R being an alkyl group as described. The 2-acyl,bicyclo [2,2,1] heptene-S is readily prepared by the Diels-Alderreaction of an alkyl vinyl ketone with cyclopentadiene.

The use of a 2-acyl, 3-halo, bicyclo [2,2,1] heptene-S in this reactionresults'in the following:

0 0R C 0R 2ROOSH RC OS HX X SOCR X being halogen and R being alkyl. TheZ-acyl, 3-halo, bicyclo [2,2,1] heptene-S may be a Diels-Alder adduct ofan alkyl p-halovinyl ketone and cyclopentadiene.

In addition, when one employs a 2,3-dicarboalkoxy bicyclo [2,2,1]heptene-S, the reaction proceeds as fol- R again being alkyl. In thiscase, the bicycloheptene is RCOSH "ice prepared by forming an adduct ofcyclopentadiene and maleic anhydride, followed by esterification of theresulting adduct to form a dialkyl ester thereof.

As indicated above, the aliphatic thioacid adds to the 5 ethyleniclinkage in the various Diels-Alder adducts descibed to form the desired[2,2,1] bicycloheptane derivatives. In the reaction of the thioacid witha 2-acyl, 3- halo, bicyclo [2,2,1] heptene-S (the adduct ofcyclopentadiene and an alkyl phalovinyl ketone), not only does theaddition occur, but the halogen atom of the bicycloheptene is displacedby the thioacyl group. The reactions proceed well without a catalyst. Ineach case, it is preferred to employ stoichiometric quantities of thereactants, i. e. l or 2 moles of aliphatic thioacid per mole ofbicycloheptene, depending upon the particular reaction involved.However, a slight excess above these amounts does no harm, and even withless than the preferred amount of aliphatic thioacid the desiredproducts may be obtained. In fact, with only one mole of the thioacidper mole of 2-acyl, 3-halo, bicyclo [2,2,1] heptene-S, the desiredaddition of the thioacyl group to the unsaturated portion of the ring,and the replacement of the halogen on the ring with another thioacylgroup both occur to a substantial degree. The disubstituted thioacylbicycloheptane thus formed is particularly unexpected in view of thedifferent reactions involved, one being addition and the otherreplacement. Since the reaction is strongly exothermic, it is preferredto mix the reactants slowly with cooling to maintain the temperature ofthe mixture below the boiling point of the thioacid.

After they have been thoroughly mixed, they are permitted to stand for ashort period, say up to an hour. The product can then readily bepurified by distillation under reduced pressure.

The invention is still further illustrated by the following exampleswhich are not intended to impose any limitation thereon.

Example I Methylvinyl ketone was reacted with cyclopentadiene to formthe adduct, Z-acetyl bicyclo [2,2,1] heptene-S,

Then 10.0 g. (.132 mole) of thioacetic acid was added dropwise to 13.2g. (.097 mole) of the adduct with cooling to keep the temperature below80 C. After all of the adduct had been added, the mixture was permittedto stand at room temperature for one hour. Thereafter, it was distilledunder vacuum to obtain 15.7 g. of

a colorless liquid boiling between 9496 C. at 0.05 mm.

The yield of this product was 76% and its analysis was as follows:

Calculated Found Example 11 Example I was repeated with 2-propionylbicyclo [2,2,1] heptene-S (the ethylvinyl ketone adduct ofcyclopentadiene). A colorless liquid boiling in the range of 107-108" C.at 0.04 mm. was thus obtained in 86% yield. The analysis of this productis given below:

Calculated Found 8.02 8.15 14.14 14.22 'nn"=1.l520

Example III The procedure of Example I was again followed with2-prop1onyl-3-chloro-bicyclo [2,2,1] heptene-S (the ethyl fl-chlorovinylketone adduct of cyclopentadiene). However, in this case 37.0 g. (0.2mole) of the adduct 1 was reacted with 20.0 g. (0.26 mole) of thioaceticacid.

30 The reaction resulted in the introduction of two thioacetyl groups tothe bicycloheptene ring, one replacing the chlorine and the other addingto the ethylenic linkage in the adduct. The product, a pale yellow,viscous liquid, was obtained in 51% yield based on thioacetic acid, andboiled in the range of 155-158 C. at 0.06 mm. Its analysis follows:

Calculated Found Example IV 2,3-dicarbobutoxy bicyclo [2,2,1] heptene-Swas prepared by esterifying carbic anhydride with butanol, carbicanhydride being an addu'ct of maleic anhydride and cyclopentadiene. Theesterified adduct was then reacted with thioacetic acid in accordancewith the procedure outlined in Example I. Upon completion of thereaction a 77% yield of a colorless liquid was obtained, boiling between157-184 C. at 0.07 mm. Analysis of the product appears below:

Calculated Found Resort may be had to such modifications and equivalentsas fall within the spirit of the invention and the scope of the appendedclaims.

What is claimed is:

1. A compound represented by the following formula:

-Ri RC OS wherein R is an alkyl radical; R1 is selected from the groupconsisting of alkyl and alkoxy radicals; R2 is selected from the groupconsisting of hydrogen and aeylthio radicals when R1 is alkyl; and R2 iscarboalkoxy when R1 is alkoxy.

2. A compound represented by the following formula:

CHsC OS 3. A compound represented by the following formula:

0 -CiHs 01130 08 4. A compound represented by the following formula:

0 ll o-clrn omcos so 0 0H;

5. A compound represented by the following formula:

0 CHaC OS ll-OCiHI No references cited.

1. A COMPOUND REPRESENTED BY THE FOLLOWING FORMULA: